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What are cell junctions?

Cell junctions regulate small-molecule trafficking between cells, the organization of cells into tissues, and the adherence of cells to each other and the extracellular matrix. Dysfunctional junctions are implicated in several diseases, including cancer, neurodegeneration, and cardiovascular dysfunction. Understanding cell junctions is fundamental to understanding disease pathology.

Gap junctions are clusters of tightly packed channels that allow small molecules (metabolites, second messengers, and ions) to travel between adjoining cells1. This molecular exchange is essential during development and differentiation; it also creates cell proliferation, tumor suppression, cell death propagation, and survival-modulating signals2. These signals include connexins, and pannexin 1 and 2, important components of synapses3. Several kinases phosphorylate connexins and alter their functions: V-src kinase, C-src kinase, PKC, MAPK, cdc2 kinase, casein kinase I, and PKA.

A number of other proteins, such as ZO-1, ZO-2, β-catenin, drebrin, α/β tubulin, caveolin-1, NOV, CIP85, and OCP2 also associate with connexins. Connexin-43 (CX43) and connexin-40 work together to form cell junctions that are essential for proper heart atrium cell function (Figure 1).

Tight junctions

Figure 2. Claudin proteins. Immunofluorescence staining of frozen mouse jejunum tissue using Mouse anti-Claudin-1 (red), and Mouse anti ZO-1 is labeled in green; nuclei are stained with DAPI (blue). Image courtesy of Jennifer Holmes and Dr. James Anderson, University of North Carolina at Chapel Hill, NC.

Tight junctions are barriers that regulate the paracellular movement of solutes down their electro-osmotic gradients. They also act as a fence that maintains differential composition of basolateral and apical membrane domains, limiting the diffusion of lipids and proteins between cellular compartments. The main components of tight junctions are claudins, occludins, and junctional adhesion molecules (JAMs). Proteins such as ZO-1, ZO-2, ZO-3, MUPP-1, and PATJ colocalize with claudin proteins and together form tight junctions (Figure 2).

Adherens junctions are the building blocks of tissue architecture. Their main components are cadherins and catenins. These proteins form cell−cell junctions (Figure 3), and can facilitate signaling pathways such as AKT, Wnt, and MAPK to govern morphogenesis, tissue homeostasis, and intercellular communication5.. Disruption of adherens junctions promotes tumor cell invasion and metastasis 6.

Desmosomes and hemidesmosomes

Desmosomes and hemidesmosomes are specialized in cell−cell and cell–extracellular matrix adhesion, respectively7. They are important in cytoskeletal organization, cell signaling, and tissue patterning. The main components of desmosomes are cadherins (desmogleins and desmocollins). Hemidesmosomes employ integrins as their primary cell adhesion proteins.